TY - JOUR
KW - Immunology
AU - Ma F
AU - Hughes TK
AU - Teles RMB
AU - Andrade PR
AU - de Andrade Silva BJ
AU - Plazyo O
AU - Tsoi LC
AU - Do T
AU - Wadsworth MH
AU - Oulee A
AU - Ochoa MT
AU - Sarno EN
AU - Luisa Iruela-Arispe M
AU - Klechevsky E
AU - Bryson B
AU - Shalek AK
AU - Bloom BR
AU - Gudjonsson JE
AU - Pellegrini M
AU - Modlin RL
AB - Granulomas are complex cellular structures composed predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated the single-cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single-cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RRs), a dynamic process whereby some patients with disseminated lepromatous leprosy (L-lep) transition toward self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions and regulated by interferon-γ and interleukin-1β. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts can each contribute to the antimicrobial response.
BT - Nature Immunology
DO - 10.1038/s41590-021-00956-8
IS - 7
LA - eng
N2 - Granulomas are complex cellular structures composed predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated the single-cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single-cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RRs), a dynamic process whereby some patients with disseminated lepromatous leprosy (L-lep) transition toward self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions and regulated by interferon-γ and interleukin-1β. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts can each contribute to the antimicrobial response.
PB - Springer Science and Business Media LLC
PY - 2021
SP - 839
EP - 850
T2 - Nature Immunology
TI - The cellular architecture of the antimicrobial response network in human leprosy granulomas
VL - 22
SN - 1529-2908, 1529-2916
ER -